Clinical research study
Tumor Necrosis Factor Antagonist Responsiveness in a United States Rheumatoid Arthritis Cohort

https://doi.org/10.1016/j.amjmed.2008.02.018Get rights and content

Abstract

Objective

The study objective was to investigate responsiveness according to whether patients satisfy eligibility criteria from randomized controlled trials of tumor necrosis factor (TNF) antagonists in a multicentered US cohort.

Methods

Biologic-naïve patients with rheumatoid arthritis who were prescribed TNF antagonists (n = 465) in the Consortium of Rheumatology Researchers of North America registry were included. Patients were stratified by whether they met eligibility criteria from 3 major TNF antagonist trials. Two cohorts were examined: Cohort A (n = 336) included patients with complete American College of Rheumatology response criteria except acute phase reactants, and cohort B (n = 129) included patients with complete response criteria. Study outcomes included modified American College of Rheumatology 20% and 50% improvement responses (cohort A) and standard American College of Rheumatology improvement (cohort B).

Results

A minority of patients (5.4%-19.4%) prescribed TNF antagonists met trial eligibility criteria and predominantly had high disease activity (78.5%-100%). For patients who met eligibility criteria in cohort A, rates of 20% improvement (52.3%-63.6%) and 50% improvement (30.8%-45.5%) were achieved. Among patients failing to meet eligibility criteria, rates of 20% improvement (16.2%-20.4%) and 50% improvement (8.9%-10.8%) were consistently inferior (P <.05 all comparisons). For cohort B, similar differences were observed.

Conclusion

This multicentered US cohort study demonstrates that the majority of patients receiving TNF antagonists would not meet trial eligibility criteria and achieve lower clinical responses. These findings highlight the tradeoff between defining treatment responsive populations and achieving results that can be generalized for broader patient populations.

Section snippets

Materials and Methods

Patients with a diagnosis of rheumatoid arthritis and no previous biologic agent use who were enrolled in the registry and prescribed a TNF antagonist for the first time were included. The study period was from March of 2002 to May of 2006. The Consortium of Rheumatology Researchers of North America registry is a prospective observational study of patients with arthritis who were enrolled by participating rheumatologists at both academic and private practice sites; the details have been

Patient and Baseline Disease Activity Characteristics

Baseline characteristics and disease activity levels of patients in cohorts A and B are summarized and compared in Table 1, showing no significant differences with the exception that patients in cohort A were less frequently rheumatoid factor positive (69.8% vs 82.8%, P = .016). Similar proportions of patients prescribed TNF antagonists in cohorts A (27.9%) and B (28.4%) had high Clinical Disease Activity Index scores at baseline. The proportion of patients in cohort A with low, moderate, and

Discussion

In this multicentered US-based cohort study of patients with rheumatoid arthritis who were prescribed TNF antagonists, we had 2 principal findings. First, we observed that less than one fifth of patients with rheumatoid arthritis in the study cohorts prescribed a TNF antagonist would have met the eligibility requirements from 3 major TNF antagonist trials, primarily because of disease activity requirements. The proportion of patients with rheumatoid arthritis satisfying requirements for trial

Conclusions

This study of a large US cohort with rheumatoid arthritis indicates that less than one fifth of patients prescribed TNF antagonists meet typical eligibility requirements from TNF antagonist trials, and that patients failing to meet these criteria achieve inferior responses. These findings highlight the tradeoff between defining a treatment-responsive population and generalizing data from randomized controlled trials to the larger population of patients with rheumatoid arthritis who are treated

Acknowledgment

Dr. Greenberg was supported by Grant Number K23AR054412 from the National Institute of Arthritis And Musculoskeletal And Skin Diseases and a Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation. Dr. Greenberg serves as Chief Scientific Officer for CORRONA.

References (33)

  • K.L. Hyrich et al.

    Predictors of response to anti-TNF-{alpha} therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register

    Rheumatology (Oxford)

    (2006)
  • F. Wolfe et al.

    Towards an epidemiology of rheumatoid arthritis outcome with respect to treatment: randomized controlled trials overestimate treatment response and effectiveness

    Rheumatology (Oxford)

    (2005)
  • M.S. Heiberg et al.

    Adalimumab plus methotrexate is more effective than adalimumab alone in patients with established rheumatoid arthritis: results from a 6-month longitudinal, observational, multicenter study

    Ann Rheum Dis

    (2006)
  • A.L. Weaver et al.

    Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy in the treatment of rheumatoid arthritis: results from the RADIUS observational registry

    Curr Med Res Opin

    (2006)
  • A. Zink et al.

    Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials

    Arthritis Rheum

    (2006)
  • W. Kievit et al.

    The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomized controlled trials and clinical practice

    Ann Rheum Dis

    (2007)
  • Cited by (26)

    • Tools and Methods for Real-World Evidence Generation: Pragmatic Trials, Electronic Consent, and Data Linkages

      2019, Rheumatic Disease Clinics of North America
      Citation Excerpt :

      The hoped-for benefits of generating evidence and obtaining it from routine care settings, as may be recorded in electronic medical record (EMR) systems, administrative claims data (eg, pharmacy refill data), mobile health, and other diverse sources, is not only to improve the generalizability of research but also to expand the available evidence for patients with significant disease heterogeneity, multimorbidity, and more severe disease manifestations than typically permitted in an RCT. For example, the proportion of rheumatoid arthritis (RA) patients seen in routine care settings who would be eligible for a typical phase 3 RCT has been estimated to be 20% or even lower.2,3 Additional factors that may affect clinical outcomes that would be irrelevant, or considered nuisance factors in an RCT, can also be studied more effectively using real-world data.

    • Comparison of Anti-TNF Treatment Initiation in Rheumatoid Arthritis Databases Demonstrates Wide Country Variability in Patient Parameters at Initiation of Anti-TNF Therapy

      2011, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      Characteristics of OH patients were compared with those of RA patients in the OBRI and REACH registries and in published American, Czech, British, Dutch, Danish, Norwegian, Swedish, Finnish, Italian, German, Spanish and Australian databases. The databases were the Consortium of Rheumatology Researchers of North America (CORRONA) (6), National Data Bank for Rheumatic Diseases (NDB) (12), Czech National Registry (13), British Society for Rheumatology Biologics Registry (BSRBR) (14), Dutch Rheumatoid Arthritis Monitoring (DREAM) (15), Danish Registry of Biological Therapies (DANBIO) (16), Norwegian Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) (17), Anti-Rheumatic Therapies in Sweden (ARTIS) (18), South Swedish Arthritis Treatment Group (SSATG) (19), The Register of Biological Treatment in Finland (ROB-FIN) (20), Lombardy Rheumatology Network registry (LORHEN) (21), German Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) (22), Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) (23), and Australian Rheumatology Association (ARAD) (24) databases. The NDB and CORRONA registries contained data from American patients only.

    • Outcome and safety of TNFα antagonist therapy in 475 consecutive outpatients (with rheumatoid arthritis or spondyloarthropathies) treated by a single physician according to their eligibility for clinical trials

      2010, Joint Bone Spine
      Citation Excerpt :

      A study in RA patients in The Netherlands [3] found that 56% of patients on average did not meet trial selection criteria, in keeping with our results. Higher rates were noted in the German RABBIT registry (67 to 79%) [29] and in the US (80%) [4]. Another limitation of our study is the subjective evaluation of effectiveness using four response categories.

    • A Comparison of Patient Characteristics and Outcomes in Selected European and U.S. Rheumatoid Arthritis Registries<sup>1</sup>

      2010, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      Comparable data were available for RABBIT, CORRONA and VARA. Only between 6 and 33% of patients in RABBIT, CORRONA and VARA would have been eligible for the clinical trials that were reported in common (17,18). Among patients who were eligible for these trials, ACR20 and ACR50 responses were comparable between the observational cohorts (RABBIT and CORRONA) and the respective clinical trials.

    View all citing articles on Scopus

    Dr Greenberg was supported by grant number K23AR054412 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and a Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation. Dr Kishimoto was funded by a fellowship grant from the Consortium of Rheumatology Researchers of North America.

    View full text